Home » 2023 » July

Monthly Archives: July 2023

Asthma and Breastfeeding

As a community pharmacist I often saw patients repeatedly ordering their blue inhalers to relieve symptoms of asthma because they were scared that the brown preventer inhalers contained steroid and would make them look like body builders. This is, of course not going to happen using inhalers correctly. Oral thrush can be common if inhaler technique is poor but simple things like rinsing the mouth after use or using a spacer can help. Talk to your specialist asthma nurse if you are struggling with symptoms.

If we add in breastfeeding it is no surprise that mothers are concerned about their medication use to control asthma but without cause. Inhalers and steroids are compatible with breastfeeding. Not only that but breastfeeding helps to minimise the risk of your baby developing asthma in the future according to new research.

The symptoms of asthma being high because of very high pollen counts coupled with the risk of thunderstorms which can be a bad combination.

I hope this factsheet taken largely from Breastfeeding and Chronic Medical Conditions helps

wendy@breastfeeding-and-medication.co.uk

https://breastfeeding-and-medication.co.uk/wp-content/uploads/2022/06/asthma-.pdf

“My asthma actually improves when feeding and I had a big decline when I weaned my 2-year-old twins. The symptoms have gone again now I’m breastfeeding my 3-month-old.”

Description

Breastfeeding protects against asthma in children up to the age of 6. Shorter duration and non-exclusivity of breastfeeding were associated with increased risks of asthma-related symptoms in pre-school children (Mukherjee 2016). Thus, mothers with asthma may be keen to breastfeed exclusively to protect their baby. In a study of 366 pregnancies, symptoms worsened in 36% of women (Schatz 1988).  Further studies by Schatz (1995) and Wendel (1996) in the United States suggest that 11–18% of pregnant women with asthma will have at least one emergency department visit for acute asthma and, of these, 62% will require hospitalisation.

Wilson et al (2022) studied 2021 mother-child dyads. Women reported the duration of any and exclusive breastfeeding and child asthma outcomes during follow-up at child aged 4 to 6 years. Outcomes included current wheeze (previous 12 months), ever asthma, current asthma (having ≥2 of current wheeze, ever asthma, medication use in past 12-24 months), and strict current asthma (ever asthma with either or both current wheeze and medication use in past 12-24 months). They showed that longer duration of exclusive breastfeeding had a protective association with child asthma.

Treatment

Asthma can be controlled during breastfeeding with:

  • inhalers (short and long-acting beta 2 agonists to relieve symptoms
  •  bronchodilators to prevent symptoms
  • compound inhalers, 
  • Prednisolone
  • Leukotriene receptor antagonists. 

Beta-adrenoreceptor agonists relieve symptoms of asthma attack such as breathlessness: E.g., Salbutamol, Bambuterol , Formoterol, Salmeterol, Terbutaline.The inhalers act locally in the lungs and limited transfer into blood let alone milk –

Oral Corticosteroids : Prednisolone – limited transfer at 40mg/day, higher doses short term. Very high doses or long term wait 4 hours after administration to breastfeed (but rarely necessary in my experience)

Inhaled Corticosteroid Inhalers prevent asthma symptoms and are used when regular use of preventer inhalers is necessary: E.g., Beclometasone, Budesonide, Fluticasone, Mometasone. Inhalers  act locally in lungs and limited transfer into blood let alone milk

Leukotrine Receptor antagonists: Montelukast – relative infant dose 0.68%. Used in children so compatible with breastfeeding. However, in September 2019 the MHRA added a caution to use in children so individual mothers may need to decide for themselves if they wish to take this drug whilst breastfeeding.

“Healthcare professionals are advised to be alert for neuropsychiatric reactions, including speech impairment and obsessive-compulsive symptoms, in adults, adolescents, and children taking montelukast. The risks and benefits of continuing treatment should be evaluated if these reactions occur. Patients should be advised to read the list of neuropsychiatric reactions in the information leaflet and seek immediate medical attention if they occur.”

Zafirlukast– relative infant dose 0.7%. Absorption slowed with food. Used in children > 12 years so compatible with breastfeeding assumed.

Theophylline/ Aminophylline – prolonged half-life in neonates (babies < 6 weeks). One reported case of irritability. Avoid if possible, especially with young babies .

There are many options of inhalers and asthma specialist should be able to make symptoms changing life a rare rather than common event. Many athletes have asthma and are able to control symptoms with the right balance of medication. For some symptoms are worse with respiratory infections, for others season affects are greater e.g., moulds, pollen from different plant affecting different times of the year.

References

  • Mukherjee M, Stoddart A, Gupta RP, Nwaru BI, Farr A, Heaven M, Fitzsimmons D, Bandyopadhyay A, Aftab C, Simpson CR, Lyons RA, Fischbacher C, Dibben C, Shields MD, Phillips CJ, Strachan DP, Davies GA, McKinstry B, Sheikh A, The epidemiology, healthcare and societal burden and costs of asthma in the UK and its member nations: analyses of standalone and linked national databases, BMC Medicine, 2016;14:113–128.
  • Schatz M, Harden K, Forsythe A, Chilingar L, Hoffman C, Sperling W, Zeiger RS, The course of asthma during pregnancy, post-partum, and with successive pregnancies: a prospective analysis, J Allergy Clin Immunol, 1988;81:509–17.
  • Schatz M, Zeiger RS, Hoffman CP, Harden K, Forsythe A, Chilingar L, Saunders B, Porreco R, Sperling W, Kagnoff M, Perinatal outcomes in the pregnancies of asthmatic women: a prospective controlled analysis, Am J Respir Crit Care Med, 1995;151:1170–4.
  • Wendel PJ, Ramin SM, Barnett-Hamm C, Rowe TF, Cunningham FG, Asthma treatment in pregnancy: a randomized controlled study, Am J Obstet Gynecol, 1996;175:150–4.
  • Wilson K, Gebretsadik T, Adgent MA, et al. The association between duration of breastfeeding and childhood asthma outcomes. Annals of Allergy, Asthma & Immunology. (https://www.annallergy.org/article/S1081-1206(22)00400-8/fulltext)
  • https://www.sps.nhs.uk/articles/using-inhaled-or-topical-corticosteroids-during-breastfeeding/

Further information: 

Asthma UK https://www.asthma.org.uk/

Breastfeeding and Chronic Medical Conditions, Wendy Jones

Norethisterone and breastfeeding

Many mothers take norethisterone to delay periods before holidays or even their wedding. Others use it to stop heavy bleeding and wish to continue to breastfeed.

Norethisterone and breastfeeding factsheet

Norethisterone 5mg tablets (Primolut N®, Utovlan®) is often prescribed to delay periods. This might be requested by the breastfeeding mother for example before a holiday or a wedding. There is little information from the research databases to support the use at this dose in breastfeeding. The only references are significantly lower doses (350mcg daily) used in progesterone only contraceptives.

It is suggested in the literature that this dose of norethisterone may reduce the quantity of breastmilk. In my experience a few mothers have noticed a temporary dip in supply but with holidays and weddings a change of routine could account for such a change. There seems to be no risk to the breastfeeding baby of a short course of medication at this dose.

Studies suggest that lower doses do not affect the composition of milk (reported in LACTMed. However Hale (Medications and Mother’s Milk states that although it is believed to be secreted into breast milk in small amounts, it may reduce lactose content and reduce overall milk volume and nitrogen/protein content, resulting in lower infant weight gain, although these effects are unlikely if doses are kept low. Norethisterone is a component of progestin oral contraceptives (Eg. Micronor™ and Brevinor ™ )

BNF : Postponement of menstruation 5mg norethisterone  3 times daily starting 3 days before expected onset (menstruation occurs 2–3 days after stopping)

N.B This information is based on anecdote and not research based studies

References

  • https://www.e-lactancia.org/breastfeeding/norethisterone/product/
  • https://www.ncbi.nlm.nih.gov/books/NBK501291/
  • Jones W Why Mother’s Medication Matters
  • Jones W Breastfeeding and Medication

Anti platelet drugs and breastfeeding

Although it is rare for a young woman to experience a heart attack, transient ischaemic attack or stroke, it does happen. They are usually prescribed anti-platelet drugs and until recently we found difficulty in providing information. However, this is the most up to date information which I have sourced and hope it helps anyone in this most difficult position.

pdf of factsheet Anti platelet drugs and breastfeeding factsheet

Anti-platelet drugs decrease platelet aggregation (stickiness) and may stop thrombus (clot)
formation. Clopidogrel is also used, sometimes alone or in combination with low-dose aspirin. There are unfortunately some mothers who, whilst breastfeeding, have a heart attack, transient ischaemic attack, stroke or other event that requires anti-platelet agents if only temporarily. Anti-platelets may also be given during investigation if such a condition is strongly suspected.
Aspirin dispersible 75 mg
Aspirin 75 mg acts by decreasing platelet stickiness irreversibly inhibiting aggregation. It is not used during treatment of thrombosis but may be used to after a myocardial infarction (MI), transient ischaemic attack and stroke or to decrease cardiovascular risk. It is also used to prevent recurrent miscarriage, with a past history of pre-eclampsia and other reasons in pregnancy (https://breastfeeding-and-medication.co.uk/fact-sheet/low-dose-aspirin-and-breastfeeding). Aspirin is not recommended during breastfeeding at analgesic doses of 600 mg four times a day, due to its association with Reye’s syndrome. However, use of low dose aspirin is considered acceptable. In the absence of the theoretical risk of association with Reye’s syndrome, aspirin would be a drug compatible with lactation due to its pharmacokinetic properties.

Milk Plasma ratio is 0.03-0.08, oral bio availability 50-75%, plasma protein binding 88-93%, relative infant dose 2.5% – 10.8%. There is no documented risk of association with Reye syndrome. Virtually all aspirin is metabolised 2-3 hours after dose.
Clopidogrel (Brand name: Plavix®)
Little is known about the levels of clopidogrel secreted into breastmilk but it’s likely to be a small amount (https://www.nhs.uk/medicines/clopidogrel/). Clopidogrel irreversibly modifies the platelet adenosine diphosphate (ADP) receptor. There are no human studies, but rat studies have shown passage into milk. This significance in human treatment is unknown. It’s unlikely that clopidogrel will cause any side effects in the baby. It is used with good tolerance in paediatrics, even in new-borns and infants (https://www.e-lactancia.org/breastfeeding/clopidogrel/product/)
The pharmacokinetics of clopidogrel show a low oral bio availability 50%, plasma protein binding 98%. Babies exposed to clopidogrel through their mother’s breastmilk should be monitored for rare bruising on the skin, blood in urine, vomit or stool.
Gastric irritation of aspirin and clopidogrel
Both aspirin and clopidogrel (Plavix ™) are gastro irritant so may need to be used with a proton pump inhibitor (PPI) for protection of the stomach. There has in the past been some concern over a potential interaction between clopidogrel and omeprazole and esomeprazole, with the anti-platelet effect of clopidogrel being diminished (https://www.gov.uk/drug-safety-update/clopidogrel-andproton-pump-inhibitors-interaction-updatedadvice#:~:text=Concomitant%20use%20of%20clopidogrel%20and,therapies%20would%20be%20mo
re%20suitable.) .

The Specialist Pharmacy Service suggest that this is a clinical decision but that
pantoprazole, lansoprazole and rabeprazole are suitable alternatives
(https://www.sps.nhs.uk/articles/do-proton-pump-inhibitors-reduce-the-clinical-efficacy-ofclopidogrel-2/). PPI medication is largely destroyed in the maternal gut and can be used during lactation.
Other anti-platelet drugs

  • Prasugrel (Effient) No studies on the transfer of prasugrel into breastmilk are available
  • Ticagrelor (Brilinta) No studies on the transfer of prasugrel into breastmilk are available
  • Dipyridamole No studies on the transfer of prasugrel into breastmilk are available

References

  • CKS Anti platelet treatment https://cks.nice.org.uk/topics/antiplatelettreatment/management/secondary-prevention-of-cvd/
  • Elactancia https://www.e-lactancia.org/
  • Finkelstein Y, Nurmohamed L, Avner M, Benson LN, Koren G. Clopidogrel use in children. J
    Pediatr. 2005 https://pubmed.ncbi.nlm.nih.gov/16291359/
  • Hale Medications and Mothers Milk Online Access
  • Kwok CS, Loke YK, Effects of proton pump inhibitors on platelet function in patients receiving
    clopidogrel: a systematic review, Drug Saf, 2012;35(2):127–39.
  • Kwok CS, Loke YK, Inconsistencies surrounding the risk of adverse outcomes with
    concomitant use of clopidogrel and proton pump inhibitors, Expert Opin Drug Saf,
    2012;11(2):275–84.
  • LactMed https://www.ncbi.nlm.nih.gov/books/NBK501922/
  • LactMed Lansoprazole https://www.ncbi.nlm.nih.gov/books/NBK501283/
  • LactMed Pantoprazole https://www.ncbi.nlm.nih.gov/books/NBK501280/
  • LactMed Rabeprazole https://www.ncbi.nlm.nih.gov/books/NBK501282/
  • Li JS, Yow E, Berezny KY, Bokesch PM, Takahashi M, Graham TP Jr, Sanders SP, Sidi D, Bonnet
    D, Ewert P, Jennings LK, Michelson AD; PICOLO Investigators. Dosing of clopidogrel for
    platelet inhibition in infants and young children: primary results of the Platelet Inhibition in
  • Children On clopidogrel (PICOLO) trial. Circulation. 2008
  • https://pubmed.ncbi.nlm.nih.gov/18195173/
  • NHS Clopidogrel. https://www.nhs.uk/medicines/clopidogrel/
  • Patient Info Antiplatelet Drugs https://patient.info/doctor/antiplatelet-drugs

Domperidone as a galactogogue

Many women report lowered milk supply ( perceived or actual) and it is a cause of many contacts to breastfeeding experts and sadly a reason many mothers turn to formula when they hadnt intended. Domperidone has for a long time been recommended to help increase supply by utilsising its ability to increase prolactin. It shouldnt be used, in my opinion unless the mother has been supported to achieve regular and effective breastfeeding. It may be needed where a premature baby has been delivered and the mother has been pumping long term – many times the supply starts to dip after 2 weeks.

pdf of this information:

https://breastfeeding-and-medication.co.uk/wp-content/uploads/2022/11/domperidone-as-a-galactogogue.pdf

I wrote a factsheet for BfN looking at all the studies on study outcomes some years ago (https://www.breastfeedingnetwork.org.uk/domperidone/ ) . This information is an update on my thoughts and in light of experience and new reports.

Some years ago I wrote a factsheet for the Breastfeeding Network on the use of domperidone as a galactagogue when the recommendations for the use of domperidone changed
https://www.breastfeedingnetwork.org.uk/domperidone/. The MHRA and EHRA recommended that domperidone be prescribed only in limited situations and at a maximum dose of 10mg three times a day for 7 days and not for breastfeeding mothers https://www.gov.uk/drug-safetyupdate/domperidone-risks-of-cardiac-side-effects.
Domperidone has long been used as a galactagogue to increase milk supply. Most of the evidence from studies lies with use to increase lactation after premature delivery but can be used later where breastfeeding got off to a difficult start such as separation of mother and baby. The research studies on domperidone and use to increase milk supply can be found in the BFN link. In my experience it had been used when adequate breastfeeding support had not been given and when feeding was not effective or frequent enough to stimulate supply. This should always be the first intervention and should be happening at every professional contact with a breastfeeding mother.
When should domperidone not be used ?
Domperidone interacts with other medication and should not be used:

  • before assessment by someone skilled in breastfeeding support alongside expressing both
    breasts, at least 8-10 times in 24 hours including overnight
  • where either mother or baby has any evidence of cardiac abnormalities and specifically
    arrhythmia
  • where either is receiving other medications known to prolong QT interval or potent CYP3A4
    inhibitors e.g., quinolone antibiotics, ketoconazole, fluconazole, macrolide antibiotics, SSRI
    antidepressants (risk low with most commonly used ( Funk 2013) tricyclic antidepressants,
    salbutamol (https://ggcmedicines.org.uk/media/uploads/ps_extra/pse_21.pdf)
  • where severe hepatic impairment has been identified in mother or baby
  • where either mother or baby has high or low levels of potassium, or low levels of magnesium (https://ggcmedicines.org.uk/media/uploads/ps_extra/pse_21.pdf)

Are there adverse effects of domperidone on babies exposed through their mother’s milk? Hale data(2022) : milk plasma ratio 0.25% (<1 regarded as compatible with breastfeeding), plasma protein binding 93% leaving only 7% which can pass into milk, oral bioavailability 13-17% because of extensive first pass metabolism, relative infant dose 0.01%-0.35% (< 10% regarded as compatible with breastfeeding. Analysis of studies not complete but indicative of low risk to babies of domperidone passing to baby and would be grounds for use in breastfeeding to be reconsidered by EHRA and MHRA.

Higher doses of domperidone to increase milk supply?
Some breastfeeding experts have used significantly higher doses of domperidone to stimulate
lactation and continued use long term without reported adverse effects (Newman J, Polokova A What Doctors Don’t Know About Breastfeeding 2022)
Tapering off dose
There are no studies that provide an evidence base on how long to continue domperidone in the case of inadequate lactation (Academy of Breastfeeding Medicine (ABM) 2018 Anecdotally, some women feel that their supply cannot be maintained without the drug, while some can reduce the dose but not stop altogether. It is possible that domperidone is acting as a placebo to boost their confidence – we do not know and should admit the limitations of the research.
After a slow withdrawal from domperidone, one study found no significant increase in formula
supplementation suggesting that once sufficient milk production is established, it is maintained even without the use of domperidone (Livingston 2007).
Knoppert (2012) showed that in 3 out of 4 women who had taken domperidone for 4 weeks at full dose, 2 weeks at reducing dose, milk supply was maintained. Although gradual weaning from the drug has become standard, there is little published evidence apart from the reports and data is based on the experience of breastfeeding specialists.
Withdrawal
Drug withdrawal symptoms consisting of insomnia, anxiety, and tachycardia were reported in a woman taking 80 mg of domperidone daily for 8 months as a galactogogue who abruptly tapered the dose over 3 days (Papastergiou 2013).

Another mother (Seeman2015) took domperidone 10 mg three times daily for 10 months as a galactagogue and stopped abruptly. After discontinuation, she experienced severe insomnia, severe anxiety, severe cognitive problems and depression.

A third postpartum woman (Doyle 2018) began domperidone 90 mg daily, increasing to 160 mg daily to increase her milk supply. Because her milk supply did not improve, she stopped nursing at 14 weeks and began to taper the domperidone dosage by 10 mg every 3 to 4 days. Seven days after discontinuing domperidone, she began experiencing insomnia, rigors, severe psychomotor agitation, and panic attacks. She restarted the drug at 90 mg daily and tapered the dose by 10 mg daily each week. At a dose of 20 mg daily, the same symptoms recurred. She required sertraline, clonazepam and reinstitution of domperidone at 40 mg daily, slowly tapering the dose over 8 weeks. Three months were required to fully resolve her symptoms.

In a fourth case (Manzouri 2017), a mother took domperidone 20 mg four times daily for 9 months to stimulate breastmilk production. She stopped breastfeeding and domperidone at that time. Two weeks later, she presented with insomnia, anxiety, nausea, headaches and palpitations. The drug was restarted at a dosage of 20 mg three times daily and began to taper the daily dosage by 10 mg every week, but after one week she complained of insomnia. Tapering was reduced to 5 mg every week, but whenever she stopped the ndrug, symptoms returned. She was able to discontinue domperidone after tapering the daily dosage by 2.5 mg weekly over 10 months A fifth case (Sharma 2022) of a mother with a history of bipolar disorder and major depression developed severe anxiety, a recurrence of depression and obsessive compulsive disorder 6 days after abruptly discontinuing domperidone 120 mg daily that she was aking as a galactogogue. Three days later, she restarted domperidone 120 mg daily and tapered her daily dose by 10 mg at weekly intervals. She took no other medications. Two weeks after discontinuing domperidone, she had signs of only mild mood disorder. Hale (2022) reports an increase in calls to InfantRisk reporting problems with withdrawal after high dose and long-term use.


This should in my opinion be discussed with the mother before prescription of the medication.
References

  • Academy of Breastfeeding Medicine ABM Clinical Protocol #9: Use of Galactogogues in
    Initiating or Augmenting Maternal Milk Production, Second Revision Bodribb W 2018.
    Breastfeed Med. 2018 Jun;13(5):307-314
  • Asztalos EV, Kiss A, daSilva OP, Campbell-Yeo M, Ito S, Knoppert D; EMPOWER Study
    Collaborative Group. Evaluating the Effect of a 14-Day Course of Domperidone on Breast
    Milk Production: A Per-Protocol Analysis from the EMPOWER Trial. Breastfeed Med. 2019
    Mar;14(2):102-107. doi: 10.1089/bfm.2018.0175. Epub 2018 Dec 13. PMID: 30543461.
  • Campbell-Yeo ML, Allen AC, Joseph KS et al. (2010) Effect of domperidone on the
    composition of preterm human breast milk. Pediatrics 125(1): e107-114.
  • da Silva OP, Knoppert DC, Angelini MM et al. (2001) Effect of domperidone on milk production in mothers of premature newborns: a randomized, double-blind, placebo-controlled
    trial. CMAJ 164(1): 17-21
  • da Silva OP, Knoppert DC. (2004) Domperidone for lactating women. CMAJ 171(7): 725
  • Doyle M, Grossman M. Case report: domperidone use as a galactagogue resulting in
    withdrawal symptoms upon discontinuation. Arch Womens Ment Health. 2018
    Aug;21(4):461-463. doi: 10.1007/s00737-017-0796-8. Epub 2017 Oct 31. PMID: 29090362.
  • Funk KA, Bostwick JR. A comparison of the risk of QT prolongation among SSRIs. Ann
    Pharmacother. 2013 Oct;47(10):1330-41)
  • Grzeskowiak LE, Smithers LG, Amir LH, Grivell RM. Domperidone for increasing breast milk
    volume in mothers expressing breast milk for their preterm infants: a systematic review and
    meta-analysis. BJOG. 2018 Oct;125(11):1371-1378. doi: 10.1111/1471-0528.15177. Epub
    2018 Mar 27. PMID: 29469929.
  • Grzeskowiak LE, Wlodek ME, Geddes DT. What Evidence Do We Have for Pharmaceutical
    Galactagogues in the Treatment of Lactation Insufficiency?-A Narrative Review. Nutrients.
    2019 Apr 28;11(5):974. doi: 10.3390/nu11050974. PMID: 31035376; PMCID: PMC6567188.
  • Hale TW and Krutsch K Medications and Mothers Milk 2022 Springer Publications
  • Ingram J, Taylor H, Churchill C, Pike A, Greenwood R, Metoclopramide or domperidone for
    increasing maternal breast milk output: a randomised controlled trial Arch Dis Child Fetal
    Neonatal Ed F2 of 5(2011). doi:10.1136/archdischild-2011-300601
  • Knoppert DC, Page A, Warren J, Carr M, Angelini M, Killick D, DaSilva OP, The Effect of Two
    Different Domperidone Doses on Maternal Milk Production published online 3 May 2012 J
    Hum Lact
  • Livingston V, Blaga Stancheva L, Stringer J. The effect of withdrawing domperidone on
    formula supplementation. Breastfeeding Med. 2007; 2:278, Abstract 3.

Follow Us

Recent Posts

Categories